DNA death predictors: What do they really tell you?

Genetic tests lay odds on killer diseases, and now a "health check" for your chromosomes spots traits that could reveal your lifespan – if it really works

MY PATERNAL grandfather lived until he was 89; his brother outdid him by a decade. My grandmothers made it to 85 and 93. My parents are both alive and kicking at 73 and 82. The only people to die young in my family were killed in wars or industrial accidents. Maybe I am just clinging to the rosy bits, but this is the information I choose to employ when predicting my own longevity. I reckon the odds are with me, and I’m not interested in knowing if I’m wrong. My greatest fear about the timing of my death is that it will come many decades after I have exhausted my supply of money.

It seems I am unusual, however. Apparently many people are thirsting for a little extra information to help them calculate how long they have left. How else can you explain the burgeoning number of commercial enterprises promising to meet that desire? Already, gene-sequencing companies such as 23andme, deCodeMe and Navigenics can do a quick scan of your risk of developing everything from lung cancer to multiple sclerosis. Now two new firms are offering to tell us how well we are ageing, based on an analysis of structures at the ends of our chromosomes called telomeres.

If these developments continue, a person’s lifespan could become as quantifiable as the shelf life of a carton of milk. So instead of parading around blissfully unaware of how long we have left, we could find out our own use-by dates. For some, this knowledge would be a burden, while others may be glad of the chance to plan their future. But whether you find the prospect of being able to foretell your own death terrifying or enticing, how realistic is it? Are these new tests really a game changer? After all, we have long been able to test for life-threatening factors such as high cholesterol and blood pressure. And while a better understanding of the biology of ageing is bound to tell us even more, surely the date of one’s death will always remain the great unknowable?

This brave new age of scientific soothsaying began a few years ago with the invention of home genetics tests that promise to alert you to things that might contribute to your ultimate decline. It couldn’t be simpler. You order the kit online, receive it through the post, collect a cheek-swab sample of DNA while sitting on your own couch and then mail it off for analysis. The news comes back by email a few weeks later. In the interests of science I gave it a go.

You decide

I soon discovered a fundamental problem&colon; the results are wide open to interpretation, making it easy to reconcile them with the views you already hold. Say you learn that, like me, you are one of those unlucky people whose risk of a heart attack goes up 60 per cent just by drinking a third cup of coffee every day. Bad though that sounds, the chances you will have a coffee-induced heart attack are still very low – and that it will kill you, lower still. Besides, if you scratch around enough, you can probably find something to offset even that small risk – such as your slightly lower-than-average odds of heart attack in general. That’s what I did. And I concluded that my grandparents might still be my best guide to my longevity.

To cut a long story short&colon; except for finding out whether you are susceptible to a few single-gene killer diseases, an inventory of genes is not very informative for anyone wanting to know how long they have got. A big list of small risks simply is not going to tell you what your odds are of making it to 95, or even 60. Will something called gastric cardia adenocarcinoma be what takes me out – my risk of getting it is 0.08 per cent, compared with an average of 0.07 per cent? Or will it be the more common melanoma, which I am ignoring because my risk is 1.3 per cent, compared with an average of 0.7 per cent?

According to Timothy Caulfield, a bioethicist and lawyer at the University of Alberta in Edmonton, Canada, who has been looking into how people react to tests like these, my attitude isn’t uncommon. “People don’t seem to do much with this risk information,” he says. “They don’t freak out. And they don’t start exercising more, eating better or getting more screening.” This should not surprise us, he adds, since we have never responded much to other more traditional predictive information, such as weight, blood pressure and cholesterol levels.

In fact, our ostrich-like attitude to genetic warning signs may even be quite sensible. Eline Slagboom at the Leiden University Medical Center in the Netherlands and her colleagues found that healthy people in their 80s and 90s were no less likely than the rest of us to carry gene variants, or alleles, known to increase the risks of heart disease, cancer and type 2 diabetes (Proceedings of the National Academy of Sciences, vol 107, p 18046). “These people from long-lived families have exactly the same numbers of deleterious alleles,” she says. The difference, however, is that they probably possess other genes that keep the dangerous ones at bay. Although none of these have been identified so far, Slagboom and colleagues have discovered four separate areas of the genome that seem to be important. They suspect the critical genes will be unglamorous, controlling aspects of metabolism, inflammation and immunity.

At 23andme, I was tested for a “longevity trait” identified by the company. Apparently I don’t possess it and have merely typical odds of living to age 95 or 100. Again, I discount this. The trait is based on two studies of small numbers of subjects and controls, with ethnicities and genders that are different from my own. Even if it does correlate with longevity in some people, why should I trust the company, given that it got a few other traits wrong, including my eye colour and whether my hair tends to curl?

Accuse me of overblown scepticism if you like, but the most evangelical proponents of genetic testing cannot get around the fact that longevity is not simply genetic. It is largely down to myriad environmental factors, including lifestyle, the effects of which cannot be measured directly. At best, the particular genes you carry will only ever explain about 25 per cent of your propensity to live a long life, says Slagboom. So can the new telomere-based tests do any better?

“At best, the particular genes you carry will only ever explain about 25 per cent of your propensity to live a long life”

Like the plastic tips at the ends of shoelaces, telomeres keep your chromosomes from fraying and getting tangled up with one another. Every time chromosomes replicate during cell division the telomeres get a bit shorter. This process starts even before you are born and about a third of their length is lost in the first 20 years of life, says Calvin Harley, president and chief scientific officer of Telome Health, based in Menlo Park, California. As we age, the shortening continues – by about 9 per cent each decade, on average. It is not clear whether some people have a higher natural rate of loss but we do know that telomeres respond to lifestyle, and that smoking, heavy drinking, obesity and stress can all shorten them a little more quickly. That is bad news because short telomeres are associated with earlier death. One study by Richard Cawthon at the University of Utah, for instance, looked at their lengths in adults over 60. People whose telomeres were shorter than average for their age cohort were 3.18 times more likely to die of heart problems and 8.54 times more likely to die from infectious disease, than those who had longer than average telomeres for their age (The Lancet, vol 361, p 393).

It is easy to see why people trying to divine their own personal expiration date would be interested in knowing how long their telomeres are, and how they compare with other people of the same age. This is exactly the information offered by a Spanish company called Life Length, based in Madrid, which began selling its €500 test a year ago. Telome Health had also planned to offer a telomere test. Back in May, co-founder Elizabeth Blackburn – a Nobel laureate for her discovery of telomerase, the enzyme that stimulates telomere elongation – told New Scientist its test would be available for under &dollar;200 by the end of the year. However, Harley now says it will only be used for research purposes for the foreseeable future. He didn’t say why.

How short is too short?

Both tests base their analysis on measurements of the telomeres in a type of white blood cell called leukocytes. “It’s a good surrogate of what’s going on throughout the body,” says Harley. Both will compare the average length of your telomeres with those of your peers, although to begin with that comparison group will be very small. However, unlike Telome Health, Life Length also provides information about the abundance of critically short telomeres. This difference in approach highlights some key gaps in our understanding of telomeres. Harley says that most studies associating telomere length with health, use measures of average length. But Life Length scientists argue that the abundance of critically short telomeres – not averages – is what individuals really need to know about. Once they shrink to a certain point, telomeres can no longer do the job of capping off the chromosomes. Critically short telomeres cause cell death and ultimately senescence, says Maria Blasco, founder of Life Length and head of the Spanish National Cancer Centre in Madrid. However, even she acknowledges that there is a lot we don’t understand yet. “We need large population studies to find the actual meaning of telomere length,” she says.

Carol Greider at Johns Hopkins University in Baltimore, Maryland, who shared the Nobel prize with Blackburn, points out that there is no consensus yet on the best technique for measuring telomeres. In fact, her work on mice found no correlation between telomere length and lifespan (Nucleic Acids Research, vol 28, p 4474) and she argues that little is known about how telomere length affects health and longevity in humans. “There’s a very wide distribution of telomere lengths,” she says, and they can vary a lot for any given age. If you fall below the first percentile, you are clearly at risk for age-related diseases, she adds, but the science hasn’t really established much beyond that. Greider concludes that telomere testing for the general public is premature.

So what about the idea that it can pinpoint your time of death? Harley plays down the notion, calling it “nonsense”. I had heard that a telomere test might be able to indicate a slim range – say, between ages 70 and 75 – with a 95 per cent chance of getting it right. But Harley insists it can only be used as an overall health indicator – a sort of “check engine” light. He likens it to a cholesterol test. I point out that at least with a cholesterol test, you know what you are measuring and so have some idea what to do if you get a bad result.

“If they could say 70 versus 90 with some degree of certainty, I think that would have an impact,” says Caulfield. People may alter their retirement age, spending patterns, travel plans and love lives. Their insurers and employers may make decisions based on this information, too, he adds.

For now, though, finding that you have short telomeres for your age might persuade you to adopt a healthier lifestyle, at best. I’m not convinced the test is for me. I already know to eat lots of greens, get lots of exercise and not live in the shadow of an industrial plume. My grandparents taught me.

What can make you live longer

BEING FEMALE

Women outlive men by an average of five years. Tom Kirkwood at Newcastle University in the UK suspects it may be because women’s bodies are better at repairing themselves.

AN ACADEMY AWARD

It is not enough to be nominated, you have to win. A study by Donald Redelmeier of the University of Toronto, Canada, compared all actors and actresses ever nominated for an Oscar. Winners lived on average 3.9 years longer (Annals of Internal Medicine, vol 134, p 955)

BEING TALL

After analysing 490 sets of skeletal remains, measuring bone length and calculating age of death from dental erosion, a UK research team concluded that tall people live longer.

In search of a longevity pill

More than a decade ago, Maria Blasco, now head of the Spanish National Cancer Centre in Madrid, discovered how to extend the lifespan of mice by 40 per cent. The secret? Telomerase, the enzyme that helps elongate the structures at the end of chromosomes called telomeres.

Telomerase is a major player in early embryonic development and fetal life, but, even before we are born, it is switched off. (The exception is in germ-line cells, which give rise to sperm or eggs.) Why the enzyme’s activity is down-regulated is not entirely understood, but it is thought to be an anti-cancer strategy&colon; although telomerase doesn’t cause cancer, once mutations occur, it helps tumours thrive. The mice in Blasco’s experiments, it should be noted, were engineered not to form tumours.

Nonetheless, there is a huge interest in the potential anti-ageing effects of telomerase and, since January 2007, a small group of people have been experimenting with a nutritional supplement called TA-65, which activates telomerase in human immune cells. The supplement is derived from the Chinese herb astragalus, and was developed by, among others, Calvin Harley, now president of Telome Health (see main story). As it happens, Harley is also one of the experimental subjects taking the TA-65.

Early results are mixed. After a year of supplementation, the average telomere length of the subjects did not increase. However, the percentage of critically short telomeres was significantly reduced (Rejuvenation Research, vol 14, p 45). Randomised controlled trials are set to follow.